| Examples of studies
using comparative approaches to cancer investigation are presented
below. Common to these investigations is the understanding
that the study of spontaneous cancers in dogs will contribute
to a better understanding of cancer in general.
In the cancer research community, the awareness
of naturally occurring cancer models is relatively limited.
Broader awareness of these naturally occurring cancer models
is needed, as are greater opportunities for collaboration
and interaction between comparative oncologists and the cancer
research community.
Several advances in the field of cancer have
been made through a comparative oncology approach. Recent
national attention has highlighted the comparative oncology
program:
Wall
Street Journal: Cancer Strides for Dogs Assist Human Therapy
Clinical
Trials Going to the Dogs: Canine Program To Study Tumor
Treatment, Biology
Mack GS. Cancer researchers usher in dog
days of medicine. Nat Med 11: 1018, 2005.
Comparative oncologists study naturally occurring
pet cancer to:
Understand environmental risks for human
cancer. Companion animals may represent sentinels for environmental
risk factors for cancer. Furthermore, these models may be
helpful for the study of agents that may prevent cancers.
- Hargis AM, Thomassen RW. Animal model: solar dermatosis
(keratosis) and solar dermatosis with squamous cell carcinoma.
Am J Pathol. 1979 Jan; 94(1):193-6.
- Reif JS, Dunn K, Ogilvie GK, et al. Passive smoking
and canine lung cancer risk. Am J Epidemiol. 1992 Feb
1; 135(3): 234-9.
- Glickman LT, Schofer FS, McKee LJ, et al. Epidemiologic
study of insecticide exposures, obesity, and risk of bladder
cancer in household dogs. J Toxicol Environ Health. 1989;
28(4): 407-14.
- Hayes HM, Tarone RE, Cantor KP. Case-control study
of canine malignant lymphoma: positive association with
dog owner’s use of 2, 4 dichlorophenoxyacetic acid
herbicides. J Natl Cancer Inst. 1991 Sep 4; 83(17): 1226-31.
- Waters DJ, Hayden DW, Bell FW, et al. Prostatic intraepithelial
neoplasia in dogs with spontaneous prostate cancer. Prostate.
1997 Feb 1; 30(2): 92-7.
- Bukowski JA, Wartenberg D, Goldschmidt M. Environmental
causes for sinonasal cancers in pet dogs and their usefulness
as sentinels of indoor cancer risk. J Toxicol Environ
Health A. 1998 Aug 7; 54(7): 579-91.
Examine genetic/familial determinants
for cancer predispositions. The study of cancer genetics
can be simplified by studies of cancer risk in breeds of dogs
and within families of dogs. Cancer genes identified in dogs
have been shown to be relevant in human familial cancers.
This work will be enhanced with the progress of the canine
genome project.
- Onions DL. A prospective survey of familial canine
lymphosarcoma. J Natl Cancer Inst. 1984 Apr; 72(4): 909-12.
- Szabo CI, Wagner LA, Francisco LV, et al. Human, canine
and murine BRCA1 genes: sequence comparison among species.
Hum Mol Genet. 1996 Sep; 5(9): 1289-98.
- Schafer KA, Kelly G, Schrader R, et al. A canine model
of familial mammary gland neoplasia. Vet Pathol. 1998
May; 35(3): 168-77.
- Jonasdottir TJ, Mellersh CS, Moe L, et al. Genetic
mapping of a naturally occurring hereditary renal cancer
syndrome in dogs. Proc Natl Acad Sci U S A. 2000 Apr 11;
97(8): 4132-7.
- Ostrander EA, Comstock KE. The domestic dog genome.
Curr Biol. 2004 Feb 3; 14(3): R98-9.
Improve our understanding of cancer
biology and to add biological relevance to genomics data in
experimental model systems. The availability of tumor
samples from large populations of dogs contributes to their
value to the study of cancer biology. The availability of
molecular techniques and information from the canine genome
project will enhance opportunities to study cancer biology
that is informative for human disease in companion animals.
- London CA, Galli SJ, Yuuki, et al. Spontaneous canine
mast cell tumors express tandem duplications in the proto-oncogene
c-kit. Exp Hematol. 1999 Apr; 27(4): 689-97.
- Prescott DM, Charles HC, Poulson JM, et al. The relationship
between intracellular and extracellular pH in spontaneous
canine tumors. Clin Cancer Res. 2000 Jun; 6(6): 2501-5.
- Thomas R, Fiegler H, Ostrander EA, et al. A canine
cancer-gene microarray for CGH analysis of tumors. Cytogenet
Genome Res. 2003; 102(1-4): 254-60.
- Catchpole B, Gould SM, Kellett-Gregory LM, et al. Development
of a multiple-marker polymerase chain reaction assay for
detection of metastatic melanoma in lymph node aspirates
of dogs. Am J Vet Res. 2003 May; 64(5): 544-9.
- Khanna C, Wan X, Bose S, et al. The membrane-cytoskeleton
linker ezrin is necessary for osteosarcoma metastasis.
Nat Med. 2004 Feb; 10(2): 182-6.
Evaluate novel therapeutic strategies.
In addition to techniques such as chemotherapy, surgery, and
radiation, approaches such as anti-angiogenesis, immunotoxins,
and general immunotherapy are now being used to fight cancer.
These novel treatments were tested first in animals.
- Kurzman ID, MacEwen EG, Rosenthal RC, et al. Adjuvant
therapy for osteosarcoma in dogs: results of randomized
clinical trials using combined liposome-encapsulated muramyl
tripeptide and cisplatin. Clin Cancer Res. 1995 Dec; 1(12):
1595-601.
- Andrawiss M, Opolon P, Benihoud K, et al. Adenovirus-mediated
gene transfer in dog prostate: a preclinical study of
a relevant model system for gene therapy of human prostatic
cancer. Prostate Cancer Prostatic Dis. 1999 Jan; 2(1):
25-35.
- Knapp DW, Glickman NW, Widmer WR, et al. Cisplatin
versus cisplatin combined with piroxicam in a canine model
of human invasive urinary bladder cancer. Cancer Chemother
Pharmacol. 2000; 46(3): 221-6.
- Khanna C, Prehn J, Hayden D, et al. A randomized controlled
trial of octreotide pamoate long-acting release and carboplatin
versus carboplatin alone in dogs with naturally occurring
osteosarcoma: evaluation of insulin-like growth factor
suppression and chemotherapy. Clin Cancer Res. 2002 Jul;
8(7): 2406-12.
- Pryer NK, Lee LB, Zadovaskaya R, et al. Proof of target
for SU11654: inhibition of KIT phosphorylation in canine
mast cell tumors. Clin Cancer Res. 2003 Nov 15; 9(15):
5729-34.
- Khanna C, Vail DM. Targeting the lung: preclinical
and comparative evaluation of anticancer aerosols in dogs
with naturally occurring cancers. Curr Cancer Drug Targets.
2003 Aug; 3(4): 265-73.
- Bergman PJ, McKnight J, Novosad A, et al. Long-term
survival of dogs with advanced malignant melanoma after
DNA vaccination with xenogeneic human tyrosinase: a phase
I trial. Clin Cancer Res. 2003 Apr; 9(4): 1284-90.
- Hansen K, Khanna C. Spontaneous and genetically engineered
animal models: use in preclinical cancer drug development.
Eur J Cancer. 2004 Apr; 40(6): 858-80.
Leading The Way
In an effort to establish the organizational infrastructure
to undertake translational clinical trials in companion animals,
the Center for Cancer Research at the National Cancer Institute,
National Institutes of Health, has formed the Comparative
Oncology Trial Consortium (COTC). This new drug development
consortium is based on collaborative relationships with accredited
schools of veterinary medicine. The COTC will initiate trials
in collaboration with NCI investigators, academic institutions,
and the pharmaceutical industry. These trials will be implemented
through the collective caseloads of the COTC membership institutions
with trial design, oversight, data management, and assessment
of biological endpoints organized by the CCR-COP. These trials
will be small in scale and will emphasize the assessment of
biological questions related to drug development. The design
of these trials will answer essential questions emerging from
the development plans of agents destined for human patients.
Current Consortium Members:
Auburn University College of Veterinary
Medicine
Small Animal Teaching Hospital
Hoerlein Hall
Auburn, AL 36849-5523
Phone: 334 - 844-4690
Fax: 334 - 844-6034
Colorado State University
College of Veterinary Medicine and Medical Sciences
1601 Campus Delivery
Fort Collins, Colorado 80523
Phone: 970-491-7051 / Fax: 970-491-2250
The Ohio State University
College of Veterinary Medicine
Veterinary Teaching Hospital
601 Vernon L. Tharp Street
Columbus, OH 43210
Phone: 614 - 292-7159
Tufts University
Cummings School of Veterinary Medicine
200 Westboro Road
North Grafton, Massachusetts 01536
Phone: 508-839-5302
University of California at Davis
School of Veterinary Medicine
Office of the Dean
University of California
One Shields Avenue
Davis, CA 95616
Phone Numbers:
Dean's Office
530-752-1360
VMTH Small Animal Clinic
530-752-1393
VMTH Large Animal Clinic
530-752-0290
University of Illinois
College of Veterinary Medicine
Small Animal Clinic
1008 West Hazelwood Drive
Urbana, IL 61802
Phone: 217 - 333-5300
University of Minnesota
College of Veterinary Medicine
Oncology Service
1365 Gortner Ave.
St. Paul, MN 55108
Phones:
Small Animal Hospital: 612-625-1919
Large Animal Hospital: 612-625-6700
University of Missouri
College of Veterinary Medicine
Veterinary Teaching Hospital
Clydesdale Hall
379 East Campus Drive
Columbia, MO 65211
Phone: 573-882-7821
Matthew J. Ryan Veterinary Hospital
University of Pennsylvania
School of Veterinary Medicine
3900 Delancey Street
Philadelphia, PA 19104-6010
Phone: 215.898.4680
Fax: 215.573.6049
University of Tennessee
The College of Veterinary Medicine
2407 River Drive, Knoxville, TN 37996-4550
Phone: 865 - 974-VETS
University of Wisconsin
School of Veterinary Medicine
2015 Linden Drive
Madison, WI 53706-1102
Phone: 608- 263-6716
The Animal Medical Center
Elmer & Mamdouha Bobst Hospital
Caspary Research Institute
510 East 62nd Street
New York, New York 10021
Phone: 212-838-8100
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